Methylphenidate has utility as a therapeutic agent, e.g. in the treatment of attention-deficient hyperactivity disorder. It was first prepared as a mixture of the erythro and threo racemates. U.S. Pat. No. 2,957,880 discloses its synthesis and also studies upon the two racemic mixtures, which revealed that the therapeutic activity resides in the threo diastereomer.
JP-A-53007627 discloses the formula EQU R*--NH--(CH.sub.2).sub.4 --CH.dbd.CH--COOR
wherein R* is the chiral auxiliary .alpha.-methylbenzylamine and R is lower alkyl. This structure is indicated as suitable for cyclisation to 1-(1-phenylethyl)-2-hydroxy-5-piperidinone, en route to antihistaminic agents.
No cyclisation is demonstrated. Further, the elemental analysis of the compound that is made, consistent with the intended product, indicates that it is actually of the formula EQU R*--NH--CO--(CH.sub.2).sub.3 --CH.dbd.CH--COOR
The fact that this is an amide may account for failure of the proposed cyclisation.
Knouzi et al, Tet. Lett. 28(16):1757-60 (1987), disclose cyclisation, again by Michael addition, of 7-arnino-2-heptenoates of the formula EQU H.sub.2 N--(CH.sub.2).sub.4 --CH.dbd.CR"--COOCH.sub.3
wherein R" is H or CH.sub.3. The resultant piperidines, and also analogous compounds, were obtained with good diastereoselectivity, except for the given compound when R" is CH.sub.3.